Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cle...Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.展开更多
The complete understanding of the growing catalog of regulatory non-coding RNAs is going to shed light in different aspects of a wide range of pathogenic mechanisms in human diseases. This review was aimed to highligh...The complete understanding of the growing catalog of regulatory non-coding RNAs is going to shed light in different aspects of a wide range of pathogenic mechanisms in human diseases. This review was aimed to highlight recent advances in the small non- coding RNA world that could have implications in the development of new strategies in medical sciences. Among the diverse group of small non-coding RNAs, we highlight the group of tRNA-derived fragments as molecules known for a long time which have recently emerged as novel regulators influencing several aspects of cell biology. We describe here recent advances in the field of tRNA-derived fragments playing key roles in the biology of some infectious agents, including E. coli, A. fumigatus, G. lamblia, Ascaris, T. cruzi, Virus, Prions and a brief overview linking them to cancer biology. Additionally, we focus on the potential implications of these molecules in future biotechnological applications in the development of new biomarkers and as new therapeutic targets.展开更多
Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular funct...Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein synthesis.SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human diseases.It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in patients.On the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer type.Recent research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous conditions.Consequently,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC.Nevertheless,current comprehension of the potential roles of snoRNAs in CRC remains limited.This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.展开更多
Liver cancer presents divergent clinical behaviors.There remain opportunities for molecular markers to improve liver cancer diagnosis and prognosis,especially since tRNA-derived small RNAs(tsRNA)have rarely been studi...Liver cancer presents divergent clinical behaviors.There remain opportunities for molecular markers to improve liver cancer diagnosis and prognosis,especially since tRNA-derived small RNAs(tsRNA)have rarely been studied.In this study,a random forests(RF)diagnostic model was built based upon tsRNA profiling of paired tumor and adjacent normal samples and validated by independent validation(IV).A LASSO model was used to developed a seven-tsRNA-based risk score signature for liver cancer prognosis.Model performance was evaluated by a receiver operating characteristic curve(ROC curve)and Precision-Recall curve(PR curve).The five-tsRNA-based RF diagnosis model had area under the receiver operating characteristic curve(AUROC)88%and area under the precision–recall curve(AUPR)87%in the discovery cohort and 87%and 86%in IV-AUROC and IV-AUPR,respectively.The seven-tsRNA-based prognostic model predicts the overall survival of liver cancer patients(Hazard Ratio 2.02,95%CI 1.36–3.00,P<0.001),independent of standard clinicopathological prognostic factors.Moreover,the model successfully categorizes patients into high-low risk groups.Diagnostic and prognostic modeling can be reliably utilized in the diagnosis of liver cancer and high-low risk classification of patients based upon tsRNA characterization.展开更多
Objective:To determine the genetic diversity of Plasmodium(P.)knowlesi isolates from Sabah,Malaysian Borneo and Peninsular Malaysia,targeting the S-type SSU rRNA gene and including aspects of natural selection and hap...Objective:To determine the genetic diversity of Plasmodium(P.)knowlesi isolates from Sabah,Malaysian Borneo and Peninsular Malaysia,targeting the S-type SSU rRNA gene and including aspects of natural selection and haplotype.Methods:Thirty-nine blood samples infected with P.knowlesi were collected in Sabah,Malaysian Borneo and Peninsular Malaysia.The S-type SSU rRNA gene was amplified using polymerase chain reaction,cloned into a vector,and sequenced.The natural selection and haplotype of the S-type SSU rRNA gene sequences were determined using DnaSP v6 and illustrated using NETWORK v10.This study's 39 S-type SSU rRNA sequences and eight sequences from the Genbank database were subjected to phylogenetic analysis using MEGA 11.Results:Overall,the phylogenetic analysis showed no evidence of a geographical cluster of P.knowlesi isolates from different areas in Malaysia based on the S-type SSU rRNA gene sequences.The S-type SSU rRNA gene sequences were relatively conserved and with a purifying effect.Haplotype sharing of the S-type SSU rRNA gene was observed between the P.knowlesi isolates in Sabah,Malaysian Borneo,but not between Sabah,Malaysian Borneo and Peninsular Malaysia.Conclusions:This study suggests that the S-type SSU rRNA gene of P.knowlesi isolates in Sabah,Malaysian Borneo,and Peninsular Malaysia has fewer polymorphic sites,representing the conservation of the gene.These features make the S-type SSU rRNA gene suitable for comparative studies,such as determining the evolutionary relationships and common ancestry among P.knowlesi species.展开更多
This editorial reviews the molecular mechanisms underlying the roles of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 16(SNHG16)in digestive system cancers based on two recent studies on lncRNAs in dige...This editorial reviews the molecular mechanisms underlying the roles of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 16(SNHG16)in digestive system cancers based on two recent studies on lncRNAs in digestive system tumors.The first study,by Zhao et al,explored how hBD-1 affects colon cancer,via the lncRNA TCONS_00014506,by inhibiting mTOR and promoting autophagy.The second one,by Li et al,identified the lncRNA prion protein testis specific(PRNT)as a factor in oxaliplatin resistance by sponging ZNF184 to regulate HIPK2 and influence colorectal cancer progression and chemoresistance,suggesting PRNT as a potential therapeutic target for colorectal cancer.Both of these two articles discuss the mechanisms by which lncRNAs contribute to the development and progression of digestive system cancers.As a recent research hotspot,SNHG16 is a typical lncRNA that has been extensively studied for its association with digestive system cancers.The prevailing hypothesis is that SNHG16 participates in the development and progression of digestive system tumors by acting as a competing endogenous RNA,interacting with other proteins,regulating various genes,and affecting downstream target molecules.This review systematically examines the recently reported biological functions,related molecular mechanisms,and potential clinical significance of SNHG16 in various digestive system cancers,and explores the relationship between SNHG16 and digestive system cancers.The findings suggest that SNHG16 may serve as a potential biomarker and therapeutic target for human digestive system cancers.展开更多
High-throughput RNAoseq has revolutionized the process of small RNA （sRNA） discovery, leading to a rapid expansion of sRNA categories. In addition to the previously wellcharacterized sRNAs such as microRNAs （miRNAs...High-throughput RNAoseq has revolutionized the process of small RNA （sRNA） discovery, leading to a rapid expansion of sRNA categories. In addition to the previously wellcharacterized sRNAs such as microRNAs （miRNAs）, piwi-interacting RNAs （piRNAs）, and small nucleolar RNA （snoRNAs）, recent emerging studies have spotlighted on tRNA-derived sRNAs （tsRNAs） and rRNA-derived sRNAs （rsRNAs） as new categories of sRNAs that bear versatile functions. Since existing software and pipelines for sRNA annotation are mostly focused on analyzing miRNAs or piRNAs, here we developed the sRNA annotation pipeline _optimized for rRNA- and tRNA-derived s_RNAs （SPORTS 1 .0）. SPORTS1.0 is optimized for analyzing tsRNAs and rsRNAs from sRNA-seq data, in addition to its capacity to annotate canonical sRNAs such as miRNAs and piRNAs. Moreover, SPORTS1.0 can predict potential RNA modification sites based on nucleotide mismatches within sRNAs. SPORTS1.0 is precompiled to annotate sRNAs for a wide range of 68 species across bacteria, yeast, plant, and animal kingdoms, while additional species for analyses could be readily expanded upon end users＇ input. For demonstration, by analyzing sRNA datasets using SPORTS1.0, we reveal that distinct signatures are present in tsRNAs and rsRNAs from different mouse cell types. We also find that compared to other sRNA species, tsRNAs bear the highest mismatch rate, which is consistent with their highly modified nature. SPORTS1.0 is an opensource software and can be publically accessed at https：//github.com/junchaoshi/sports1.0.展开更多
Flower development plays vital role in horticultural plants.Post-transcriptional regulation via small RNAs is important for plant flower development.To uncover post-transcriptional regulatory networks during the flowe...Flower development plays vital role in horticultural plants.Post-transcriptional regulation via small RNAs is important for plant flower development.To uncover post-transcriptional regulatory networks during the flower development in Dimocarpus longan Lour.‘Shixia’,an economically important fruit crop in subtropical regions,we collected and analyzed sRNA deep-sequencing datasets and degradome libraries Apart from identifying miRNAs and phased siRNA generating loci(PHAS loci),120 hairpin loci,producing abundant sRNAs,were identified by in-house protocols.Our results suggested that 56 miRNA-target pairs,2221-nt-PHAS loci,and 111 hairpin loci are involved in posttranscriptional gene silencing during longan reproductive development.Lineage-specific or species-specific post-transcriptional regulatory modules have been unveiled,including miR482-PHAS and miRN15.miR482-PHAS might be involved in longan flower development beyond their conserved roles in plant defense,and miRN15 is a novel miRNA likely associated with a hairpin locus(HPL-056)to regulate strigolactone receptor gene DWARF14(D14)and the biogenesis of phasiRNAs from D14.These small RNAs are enriched in flower buds,suggesting they are likely involved in post-transcriptional regulatory networks essential for longan flower development via the strigolactone signaling pathway.展开更多
基金supported by the National Natural Science Foundation of China,No.81870979(to JJL),No.81271366(to MLY)the National Key R&D Program of China,No.2018YFF0301104(to JJL)+4 种基金the Special Fund for Basic Scientific Research of Central Public Research Institutes of China,No.2018CZ-1(to JJL)the Basic Scientific Research Foundation of China Rehabilitation Research Center,No.2018ZX-30(to FG)the Scientific Research Foundation of CRRC,No.2012C-1(to JJL)the Major Science and Technology Project of Beijing of China,No.D161100002816004(to JJL)the Special Capital Health Research and Development of China,No.2018-1-6011(to JJL)
文摘Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.
文摘The complete understanding of the growing catalog of regulatory non-coding RNAs is going to shed light in different aspects of a wide range of pathogenic mechanisms in human diseases. This review was aimed to highlight recent advances in the small non- coding RNA world that could have implications in the development of new strategies in medical sciences. Among the diverse group of small non-coding RNAs, we highlight the group of tRNA-derived fragments as molecules known for a long time which have recently emerged as novel regulators influencing several aspects of cell biology. We describe here recent advances in the field of tRNA-derived fragments playing key roles in the biology of some infectious agents, including E. coli, A. fumigatus, G. lamblia, Ascaris, T. cruzi, Virus, Prions and a brief overview linking them to cancer biology. Additionally, we focus on the potential implications of these molecules in future biotechnological applications in the development of new biomarkers and as new therapeutic targets.
基金the National Natural Science Foundation of China,No.82273457Guangdong Basic and Applied Basic Research Foundation,No.2021A1515012180 and No.2023A1515012762+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040and Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein synthesis.SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human diseases.It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in patients.On the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer type.Recent research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous conditions.Consequently,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC.Nevertheless,current comprehension of the potential roles of snoRNAs in CRC remains limited.This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.
基金This work was also supported by the NIH Grants(No.5P30GM114737,P20GM103466,U54MD007584 and 2U54MD007601)Natural Science Foundation of Hubei Province(No.2019CFB417).
文摘Liver cancer presents divergent clinical behaviors.There remain opportunities for molecular markers to improve liver cancer diagnosis and prognosis,especially since tRNA-derived small RNAs(tsRNA)have rarely been studied.In this study,a random forests(RF)diagnostic model was built based upon tsRNA profiling of paired tumor and adjacent normal samples and validated by independent validation(IV).A LASSO model was used to developed a seven-tsRNA-based risk score signature for liver cancer prognosis.Model performance was evaluated by a receiver operating characteristic curve(ROC curve)and Precision-Recall curve(PR curve).The five-tsRNA-based RF diagnosis model had area under the receiver operating characteristic curve(AUROC)88%and area under the precision–recall curve(AUPR)87%in the discovery cohort and 87%and 86%in IV-AUROC and IV-AUPR,respectively.The seven-tsRNA-based prognostic model predicts the overall survival of liver cancer patients(Hazard Ratio 2.02,95%CI 1.36–3.00,P<0.001),independent of standard clinicopathological prognostic factors.Moreover,the model successfully categorizes patients into high-low risk groups.Diagnostic and prognostic modeling can be reliably utilized in the diagnosis of liver cancer and high-low risk classification of patients based upon tsRNA characterization.
基金This study was supported by the Ministry of Higher Education,Malaysia(FRGS0322-SG-1/2013)Universiti Malaysia Sabah(GUG0521-2/2020).
文摘Objective:To determine the genetic diversity of Plasmodium(P.)knowlesi isolates from Sabah,Malaysian Borneo and Peninsular Malaysia,targeting the S-type SSU rRNA gene and including aspects of natural selection and haplotype.Methods:Thirty-nine blood samples infected with P.knowlesi were collected in Sabah,Malaysian Borneo and Peninsular Malaysia.The S-type SSU rRNA gene was amplified using polymerase chain reaction,cloned into a vector,and sequenced.The natural selection and haplotype of the S-type SSU rRNA gene sequences were determined using DnaSP v6 and illustrated using NETWORK v10.This study's 39 S-type SSU rRNA sequences and eight sequences from the Genbank database were subjected to phylogenetic analysis using MEGA 11.Results:Overall,the phylogenetic analysis showed no evidence of a geographical cluster of P.knowlesi isolates from different areas in Malaysia based on the S-type SSU rRNA gene sequences.The S-type SSU rRNA gene sequences were relatively conserved and with a purifying effect.Haplotype sharing of the S-type SSU rRNA gene was observed between the P.knowlesi isolates in Sabah,Malaysian Borneo,but not between Sabah,Malaysian Borneo and Peninsular Malaysia.Conclusions:This study suggests that the S-type SSU rRNA gene of P.knowlesi isolates in Sabah,Malaysian Borneo,and Peninsular Malaysia has fewer polymorphic sites,representing the conservation of the gene.These features make the S-type SSU rRNA gene suitable for comparative studies,such as determining the evolutionary relationships and common ancestry among P.knowlesi species.
文摘This editorial reviews the molecular mechanisms underlying the roles of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 16(SNHG16)in digestive system cancers based on two recent studies on lncRNAs in digestive system tumors.The first study,by Zhao et al,explored how hBD-1 affects colon cancer,via the lncRNA TCONS_00014506,by inhibiting mTOR and promoting autophagy.The second one,by Li et al,identified the lncRNA prion protein testis specific(PRNT)as a factor in oxaliplatin resistance by sponging ZNF184 to regulate HIPK2 and influence colorectal cancer progression and chemoresistance,suggesting PRNT as a potential therapeutic target for colorectal cancer.Both of these two articles discuss the mechanisms by which lncRNAs contribute to the development and progression of digestive system cancers.As a recent research hotspot,SNHG16 is a typical lncRNA that has been extensively studied for its association with digestive system cancers.The prevailing hypothesis is that SNHG16 participates in the development and progression of digestive system tumors by acting as a competing endogenous RNA,interacting with other proteins,regulating various genes,and affecting downstream target molecules.This review systematically examines the recently reported biological functions,related molecular mechanisms,and potential clinical significance of SNHG16 in various digestive system cancers,and explores the relationship between SNHG16 and digestive system cancers.The findings suggest that SNHG16 may serve as a potential biomarker and therapeutic target for human digestive system cancers.
基金supported by Start-up funds for Zhou and Chen labs from Reno School of Medicine,University of Nevada and from the National Institutes of Health,United States(Grant Nos.R01DK091336 and P01DK041315 to KMSGrant Nos.R01HD092431 and P30GM110767-03 to QC)
文摘High-throughput RNAoseq has revolutionized the process of small RNA （sRNA） discovery, leading to a rapid expansion of sRNA categories. In addition to the previously wellcharacterized sRNAs such as microRNAs （miRNAs）, piwi-interacting RNAs （piRNAs）, and small nucleolar RNA （snoRNAs）, recent emerging studies have spotlighted on tRNA-derived sRNAs （tsRNAs） and rRNA-derived sRNAs （rsRNAs） as new categories of sRNAs that bear versatile functions. Since existing software and pipelines for sRNA annotation are mostly focused on analyzing miRNAs or piRNAs, here we developed the sRNA annotation pipeline _optimized for rRNA- and tRNA-derived s_RNAs （SPORTS 1 .0）. SPORTS1.0 is optimized for analyzing tsRNAs and rsRNAs from sRNA-seq data, in addition to its capacity to annotate canonical sRNAs such as miRNAs and piRNAs. Moreover, SPORTS1.0 can predict potential RNA modification sites based on nucleotide mismatches within sRNAs. SPORTS1.0 is precompiled to annotate sRNAs for a wide range of 68 species across bacteria, yeast, plant, and animal kingdoms, while additional species for analyses could be readily expanded upon end users＇ input. For demonstration, by analyzing sRNA datasets using SPORTS1.0, we reveal that distinct signatures are present in tsRNAs and rsRNAs from different mouse cell types. We also find that compared to other sRNA species, tsRNAs bear the highest mismatch rate, which is consistent with their highly modified nature. SPORTS1.0 is an opensource software and can be publically accessed at https：//github.com/junchaoshi/sports1.0.
基金funded by the National Key Research and Developmental Program of China(Grant No.2018YFD1000104)supported by awards from the National Natural Science Foundation of China(Grant Nos.32002009 and 32072547)The Special Support Program of Guangdong Province(Grant No.2019TX05N193).
文摘Flower development plays vital role in horticultural plants.Post-transcriptional regulation via small RNAs is important for plant flower development.To uncover post-transcriptional regulatory networks during the flower development in Dimocarpus longan Lour.‘Shixia’,an economically important fruit crop in subtropical regions,we collected and analyzed sRNA deep-sequencing datasets and degradome libraries Apart from identifying miRNAs and phased siRNA generating loci(PHAS loci),120 hairpin loci,producing abundant sRNAs,were identified by in-house protocols.Our results suggested that 56 miRNA-target pairs,2221-nt-PHAS loci,and 111 hairpin loci are involved in posttranscriptional gene silencing during longan reproductive development.Lineage-specific or species-specific post-transcriptional regulatory modules have been unveiled,including miR482-PHAS and miRN15.miR482-PHAS might be involved in longan flower development beyond their conserved roles in plant defense,and miRN15 is a novel miRNA likely associated with a hairpin locus(HPL-056)to regulate strigolactone receptor gene DWARF14(D14)and the biogenesis of phasiRNAs from D14.These small RNAs are enriched in flower buds,suggesting they are likely involved in post-transcriptional regulatory networks essential for longan flower development via the strigolactone signaling pathway.
